Studies find existing and experimental drugs active against mers-coronavirus

[Emily]

Full text available for free.

http://aac.asm.org/content/early/201...36-14.abstract

Repurposing of clinically developed drugs for treatment of Middle East Respiratory Coronavirus Infection

Julie Dyalla,
Christopher M. Colemanb,
Brit J. Harta,
Thiagarajan Venkataramanb,
Michael R. Holbrooka,
Jason Kindrachuka,
Reed F. Johnsonc,
Gene G. Olinger Jr.a,
Peter B. Jahrlinga,c,
Monique Laidlawd,
Lisa M. Johansend,
Calli M. Leare,
Pamela J. Glasse,
Lisa E. Hensleya and
Matthew B. Friemanb#

+ Author Affiliations

Integrated Research Facility, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Frederick, Maryland, USAa
Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, Maryland, USAb
Emerging Viral Pathogens Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Frederick, Maryland, USAc
Zalicus Inc, Cambridge, Massachusetts, USAd
United States Army Medical Research Institute of Infectious Diseases, Frederick, Maryland, USAe

ABSTRACT

Outbreaks of emerging infections present the unique challenge of trying to select appropriate pharmacologic treatments in the clinic with little time available for drug testing and development. Typically clinicians are left with general supportive care and often untested convalescent plasma as available treatment options. Repurposing of approved pharmaceutical drugs for new indications presents an attractive alternative to clinicians, researchers, public health agencies, drug developers and funding agencies. Given development times and manufacturing requirements for new products, repurposing of existing drugs is likely the only solution for outbreaks due to emerging viruses. In the studies described here, a library of 290 compounds was screened for antiviral activity against Middle Eastern respiratory syndrome-coronavirus (MERS-CoV) and severe acute respiratory syndrome-coronavirus (SARS-CoV). Selection of compounds for inclusion in the library was dependent on current or previous FDA-approval or advanced clinical development. Some drugs were included that had a well-defined cellular pathway as target. In total, 27 compounds with activity against both MERS-CoV and SARS-CoV were identified. The compounds belong to thirteen different classes of pharmaceuticals including; inhibitors of estrogen receptors used for cancer treatment and inhibitors of dopamine receptor used as antipsychotics. The drugs identified in these screens provide new targets for in vivo studies as well as incorporation into ongoing clinical studies.

[Gert van der Hoek]

Studies find existing and experimental drugs active against mers-coronavirus

STUDIES FIND EXISTING AND EXPERIMENTAL DRUGS ACTIVE AGAINST MERS-CORONAVIRUS

WASHINGTON, DC – May 19, 2014 – A series of research articles published ahead of print in the journal Antimicrobial Agents and Chemotherapy have identified a number of existing pharmaceutical drugs and compounds under development that may offer effective therapies against Middle East Respiratory Syndrome (MERS).

In the first study, researchers screened a library of 290 pharmaceutical drugs, either FDA-approved or in advanced clinical development for antiviral activity against the MERS coronavirus (MERS-CoV) and severe acute respiratory syndrome coronavirus (SARS-CoV) in cell culture. They found 27 compounds that were active against both viruses including some cancer drugs and antipsychotics.

“Repurposing of approved pharmaceutical drugs for new indications presents an attractive alternative to the normal paradigm of huge library screening against a specific viral enzyme,” says author Matthew Frieman of the University of Maryland Medical School. “Given development times and manufacturing requirements for new products, repurposing of existing drugs is likely the best solution to rapidly identify therapeutics for outbreaks due to emerging viruses.”

Researchers from the National Institutes of Health, the United States Army Medical Research Institute of Infectious Diseases and Zalicus Inc., Cambridge MA, were also involved in the study. A copy of the manuscript can be found online at http://bit.ly/asmtip0514e.

In the second study, researchers collaborating in the European antiviral research program SILVER (www.silver-europe.com) used a similar methodology to screen a library of 348 FDA-approved drugs for anti-MERS-CoV activity in cell culture. They identified four compounds that inhibited MERS-CoV, SARS-CoV and Human Coronavirus 229E at relatively low concentrations. Two of the compounds were also identified by the U.S. study: the antimalarial drug chloroquine and the antipsychotic chlorpromazine.

“Although their therapeutic potential (alone or in combination) remains to be assessed in animal models, our findings may offer a starting point for treatment of patients infected with zoonotic coronaviruses like MERS-CoV,” says corresponding author Eric Snijder of Leiden University Medical Center, the Netherlands. Researchers from the Rega Institute for Medical Research in Leuven, Belgium and the Erasmus Medical Center in Rotterdam, the Netherlands were also involved in the study.

A copy of the manuscript can be found online at http://bit.ly/asmtip0514f.

The third and final study finds that an experimental compound, previously shown to block SARS-CoV replication, can inhibit replication of two other coronaviruses, MERS-CoV and mouse hepatitis virus.

"This study shows that it is possible to target multiple coronaviruses through broad-spectrum inhibitors," says corresponding author Stefan Sarafianos of the Bond Life Sciences Center at the University of Missouri, an author on the study. “This compound could serve as a lead for the development of effective broad-spectrum anti-coronavirus drugs.”

Researchers from the University of Maryland Medical School and the University of Pennsylvania School of Medicine also contributed to the research. The manuscript can be found online at http://bit.ly/asmtip0514g.

ASM

[Shannon Bennett]

Re: Studies find existing and experimental drugs active against mers-coronavirus

This should be a must read for medical professionals who have MERS patients or think they might.

I read the USAMRID paper in its entirety and found it to be intriguing. While all of the tests were done in vitro it does offer hope of new and better results then the former use of interferon along with supportive care.